Safety and efficacy of ciltacabtagene autoleucel for relapsed/refractory multiple myeloma: a CIBMTR study

Ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, was approved in 2022 for heavily pretreated relapsed/refractory multiple myeloma (RRMM). This study evaluates the safety and efficacy of cilta-cel in RRMM patients reported to the Center for International Blood and Marrow Transplant Research registry between March 2022 and December 2023 who met commercial release specifications. Among 595 patients, median age was 64 years, 57% were male, and 70% had ≥1 comorbidity. Extramedullary disease and marrow plasma cell burden ≥ 50% were present in 13% and 14% of patients, respectively. The median number of prior lines of therapy was 7 and 8% had received prior BCMA-directed therapy. Median follow-up was 12 months (range, 1-25 months). Cytokine release syndrome occurred in 80% (≥ grade 3: 4%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (≥ grade 3: 4%). Non-ICANS neurotoxicity was seen in 5% (n = 31), including Parkinsonism in 2.7% (n = 16) and cranial nerve palsies in 2.5% (n = 15), primarily cranial nerve VII (n = 12/15). Infections occurred in 47% and treatment-related mortality was 5%. The best overall response rate was 87%, with ≥ very good partial response rate in 75%, and ≥ complete response rate in 35%. Estimated 12-month progression-free and overall survival were 73% (95% CI: 68-77%) and 85% (95% CI: 81-88%), respectively. This represents the largest standard-of-care (SOC) study of cilta-cel in RRMM patients to date. Despite advanced disease and high comorbidity burden, cilta-cel demonstrated favorable safety and efficacy, supporting its use in clinical practice.